6.2 Toxicology and Exposure
In addition to the brief overview of lead toxicology and exposure presented here, more information is available in the ITRC RISK-3 document, which includes links to USEPA’s lead resources. Additionally, see Using Bioavailability Information in Risk Assessment for more information about lead risk assessment.
6.2.1 Environmentally Relevant Exposures
Ingestion of lead-contaminated fine soil and dust particulates is the primary pathway of human lead exposure from environmental sources (NTP 2012; Laidlaw et al. 2014; Lanphear et al. 1998; 2003). Lead-based paint is considered the major source of high-dose lead poisoning in the United States (CDC 2005). Dust inhalation, ingestion of contaminated soil, ingestion of contaminated food or drink, use of cookware containing lead, traditional and home medical remedies (Los Angeles Department of Public Health 2016), and some traditional cosmetics, such as kohl, a lead sulfide mineral based eyeliner (FDA 2016) also contribute to lead exposure.
188.8.131.52 Ingestion Read More
- incompletely washed produce grown in lead-contaminated soil
- dust settling in or on food and drink or dishes and glasses
- intentional ingestion of soil by young children or people with pica disorder (compulsive soil eaters)
The absorption of lead following ingestion depends on the solubility (bioaccessibility) of lead in the gastrointestinal system as well as the presence or absence of other bioactive agents in the gut. In vitro lead bioaccessibility has been studied in simulated gastric and intestinal phases. These studies conclude that the gastric phase controls lead dissolution from soil and correlates more closely to in vivo animal test results (Ruby et al. 1992; Drexler and Brattin 2007; USEPA 2007c; Juhasz et al. 2009; Smith et al. 2011).
184.108.40.206 Inhalation Read More
220.127.116.11 Dermal Read More
Toxicokinetics addresses the disposition of a chemical in humans or animals after exposure occurs. Toxicokinetic studies include an evaluation of the routes and mechanisms of absorption, patterns of distribution throughout the body, metabolism of the chemical, and excretion of metabolites or the unchanged chemical. A thorough review of lead toxicokinetics is included in the Agency for Toxic Substance and Disease Registry (ATSDR) toxicological profile for lead (ATSDR 2007b).
18.104.22.168 Absorption Read More
In human studies, recommended nutritional levels of calcium, phosphorus, and fiber reduced lead absorption (Blake and Mann 1983; James, Hilburn, and Blair 1985). Elevated levels of calcium and phosphorus combined reduced lead absorption more than increased levels of calcium or phosphorus alone (Blake and Mann 1983) and (Heard, Chamberlain, and Sherlock 1983). In the U.S. National Health and Nutrition Examination Survey, children with lower intakes of dietary calcium had increased levels of lead in their blood (Mahaffey, Gartside, and Glueck 1986). Lead may also be reintroduced into the bloodstream at times of calcium deficiency or stress (for example, pregnancy, lactation, or osteoporosis). At these times, the body withdraws calcium from internal stores along with any sequestered lead.
After inhalation, absorption of lead deposited in the respiratory tract may vary and be as high as 95%, depending on the particle size, solubility of the lead species, nose or mouth breathing, and other factors. “In adults about 35-40% of inhaled lead dust is deposited in the lungs, and about 95% of that goes into the blood stream” (Merrill, Morton, and Soileau 2007).
22.214.171.124 Distribution Read More
126.96.36.199 Metabolism Read More
188.8.131.52 Excretion Read More
Toxicodynamics addresses the toxicological effects of a chemical in humans and other animals. A thorough review of lead toxicodynamics is included in the ATSDR toxicological profile for lead (NTP 2012).
184.108.40.206 Systemic Effects Read More
Table 6‑1. Effects of lead exposure on human organ systems (adapted from ATSDR 2007b, Table 3-1)
|Exposure Duration||Target Organ||Blood Lead Concentration (µg/dL)||Effects|
|Kidney||48–80||Generally reversible, including tubular dysfunction and nephritis|
|Neurological system||80–100||Encephalopathy in children|
|Liver||Various||Inhibition of heme synthesis|
|Gastrointestinal system||60–400||Cramps, vomiting, anorexia, and constipation|
|Neurological system||40–120||Various neurological effects, including dizziness, fatigue, sleep disturbance, headache, irritability, lethargy, malaise, slurred speech and convulsions. Muscle weakness, paresthesia, ataxia, tremors, and paralysis may also occur.|
|> 2||In children, developmental lead neurotoxicity and IQ decrements|
|Kidney||Various||Nephropathy, including glomerular sclerosis, interstitial fibrosis, proximal tubular nephropathy, and decreased glomerular filtration rate|
|Gastrointestinal system||40–200||Nausea, vomiting, anorexia, constipation, and abdominal cramps in children and adults|
220.127.116.11 Reproductive and Developmental Effects Read More
Numerous studies have shown cognitive impairment at BLL above 10 µg/dL (CDC 2012). In addition, a decline of 1.37 IQ points for each 1 µg/dL increase in BLL under 10 µg/dL has been calculated (Canfield et al. 2003). In children, increasing BLL was significantly associated with decreasing body stature and head circumference (Ballew et al. 1999). In children, increased BLL is positively correlated with increased dental cavities (Moss, Lanphear, and Auinger 1999). Encephalopathy (impaired brain function) in children was associated with BLL of 90 to 800µg/dL (mean 330 µg/dL), with death occurring at a mean of 327 µg/dL (NAS 1972). Lead toxicology is an area of ongoing research and regulatory evaluation, the details of which are beyond the scope of this document.
18.104.22.168 Genotoxic Effects Read More
22.214.171.124 Carcinogenicity Read More
6.2.4 Factors that May Reduce Lead Bioavailability from Soil
In general, the bioavailability of lead-contaminated soil is lower than the bioavailability of lead in foodstuffs (Zia et al. 2011). The solubility of lead-bearing minerals or precipitates, the extent of lead desorption from soil particles in the gut, or both are the primary mechanisms that mitigate the bioavailability of ingested lead-contaminated soil. Once ingested, the fraction of lead mineral dissolution or desorption, or both from soil relative to the lead absorption across the intestinal epithelium defines the limiting process crucial to quantifying lead oral bioavailability. Lead mineral solubility and soil desorption are discussed separately, as are in vitro approaches.
Different mineral species of lead have different dissolution constants and dissolve under acidic gut conditions with variable rates and extents. Thus, both mineral equilibria and dissolution kinetics are important considerations because bioavailability may or may not reflect equilibrium conditions, which depend on the mineral surface area and gut retention time. These conditions are reflected in the solubility product constant (Ksp), which is the equilibrium constant for a mineral dissolving in a solution (water, soil, or gastric). The log value of Ksp represents the molar equilibrium concentration in solution, and in general the more soluble a given mineral, the faster dissolution occurs. The solubility products for numerous lead minerals have been recorded and are presented in Table 6-2. As log Ksp decreases, the less soluble the mineral is in solution.
Table 6‑2. Solubility products of select minerals (Lindsay 1979)
The soil matrix can adsorb lead or promote lead mineral formation when lead concentrations are above mineral saturation, indices greatly affecting lead oral bioavailability. Both electrostatic reactions with negatively charged soil surfaces and covalent reactions with soil organic matter (SOM) and amorphous iron, manganese, and aluminum oxides are relevant to varying extent. Lead typically exhibits an S-shaped adsorption curve as a function of pH on soil minerals and SOM. Thus, at a low pH, lead adsorption is limited (more in solution), adsorption sharply increases between pH 5 to 7, and maximum adsorption occurs beyond pH 7. Under gut conditions, both mineral and adsorbed forms of lead can be released into the gastrointestinal solution as freely dissolved ions (in addition to other elements in the matrix) because of the acidic conditions. Upon transfer to the intestinal tract, where pH is higher, the precipitation of amorphous oxide minerals may promote readsorption of lead to those minerals, which in turn limits absorption into the body (Beak et al. 2006b; 2008). Consequently, most lead in vitro bioaccessibility methods demonstrate that the gastric phase better predicts RBA than simulated conditions of the intestinal tract. Lead IVBA in a gastric assay is strongly correlated with in vivo RBA, even though lead is absorbed in the small intestine (Drexler and Brattin 2007).